Molbank 2007, M551 |
Eglė Nedzelskytė a, Vytas Martynaitis a, Algirdas Šačkus a, Gernot A. Eller b and Wolfgang Holzer b, *
a Institute of Synthetic Chemistry,
Kaunas University of Technology, Radvilėnų pl. 19,
LT-50254 Kaunas, Lithuania
b Department of Drug and Natural
Product Synthesis, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria
* Author to whom correspondence should be addressed. Tel: +43-1-4277-55623; E-mail: [email protected]
Received: 30 January 2007 /
Accepted: 15 February 2007 / Published: 30 May 2007
Keywords: 1-phenylpyrazol-3-ol,
bromination, O-acetylation,
NMR spectroscopy
Abstract: Dependent
on the reaction conditions, 1-phenylpyrazol-3-ol and bromine give either
4-bromo-1-phenylpyrazol-3-ol (2a) or 4-bromo-1-(4-bromophenyl)pyrazol-3-ol
(2b). Treatment of 2a or 2b with refluxing acetic anhydride leads to the
corresponding O-acetyl derivatives 3a
and 3b, respectively. Detailed spectroscopic data (1H NMR, 13C
NMR, 15N NMR, MS, IR) for 2b, 3a and 3b are
presented.
In the
course of investigations regarding Pd-catalyzed cross coupling reactions with halopyrazoles [1], we prepared 4-bromo-1-phenylpyrazol-3-ol
(2a) via reaction of
1-phenylpyrazol-3-ol (1) with one equivalent of bromine in high yield similarly
to a previously described procedure [2]. In this respect it seemed interesting
for us, if treatment of 1 with an excess of Br2 would lead to a dibromination product (introduction of a bromo atom also into the phenyl ring) and thus to a synthon with two different targets for further C每C bond
formation. Such a behaviour was reported in a related case, namely in the bromination of 1-phenylpyrazole, where the use of excess
bromine together with severe reaction conditions was found to give 15%
4-bromo-1-(4-bromphenyl)pyrazole besides the main
product 4-bromo-1-phenylpyrazole (65%) [3].
Scheme 1
We found
that treatment of 1 with 3 equivalents of bromine in a solution of boiling
carbon tetrachloride gave the dibromination product
2b in 82% yield (Scheme 1). The structure of 2b was unambiguously determined by
spectroscopic methods (1H, 13C, and 15N NMR,
MS) and CHN analysis. Furthermore, treatment of 2a and 2b with boiling acetic
anhydride afforded the corresponding O-acetyl
products 3a and 3b in high yield (Scheme 2).
Scheme 2
4-Bromo-1-(4-bromophenyl)-1H-pyrazol-3-ol (2b)
To a well
stirred solution of hydroxypyrazole 1 [4] (1 g, 6.25 mmol) in carbon tetrachloride (30 mL)
a solution of bromine (0.32 mL, 6.25 mmol) in carbon tetrachloride (8 mL)
was added dropwise during 1 h, and stirring was
continued for 2 h at room temperature. Then the reaction temperature was
increased to reach reflux temperature within 1 h while adding a second
equivalent of bromine (0.32 mL, 6.25 mmol) in carbon tetrachloride (8 mL).
After the addition was complete, stirring was continued for further 5 h at
reflux temperature. Then another equivalent of bromine (0.32 mL, 6.25 mmol) in carbon
tetrachloride (8 mL) was added dropwise
during 1 h, and stirring was continued for further 9 h at reflux temperature.
The reaction mixture was then allowed to cool to room temperature; the
precipitated solid was filtered off, washed with carbon tetrachloride (15 mL), and recrystallized from
aqueous ethanol to afford 1.63 g (82%) of pure 2b.
Melting point:
199每201 ∼C, yellowish crystals.
1H NMR (300 MHz, DMSO-d6) [6]: 汛 (ppm) 11.07 (s,
13C NMR (75 MHz, DMSO-d6) [6]: 汛 (ppm) 159.6 (C-3, 3J(C-3,H-5) = 8.8 Hz), 138.5 (Ph C-1), 132.2 (Ph C-3,5), 128.7 (C-5,
1J = 195.0 Hz), 118.6 (Ph
C-2,6), 117.3 (Ph C-4), 82.7 (C-4, 2J(C-4,H-5) = 5.0 Hz).
15N NMR (50 MHz, DMSO-d6) [7]: 汛 (ppm) −119.4 (N-2), −189.4 (N-1).
MS (m/z, %)
[8]: 320 (M+, 49), 318 (M+, 100), 316 (M+,
45), 239 (22), 237 (21), 157 (23), 157 (23), 155 (19).
Elemental
Analysis: Calculated for C9H6Br2N2O
(317.96): C, 34.00%; H, 1.90%; N, 8.81%. Found: C, 34.24%; H, 1.95%; N, 8.64%.
4-Bromo-1-phenyl-1H-pyrazol-3-yl acetate (3a)
Bromopyrazole 2a (1.91 g, 8 mmol) 每 which had been prepared
by treatment of hydroxypyrazole 1 with one equivalent
of bromine at room temperature following a known procedure [2] 每 and excess
acetic anhydride (25 mL) were heated to reflux for 30
min. Then, H2O (15 mL) was added and the
solution was stirred for further 30 min. The mixture was poured into ice-water
(50 mL) and stirred for 30 min. Then the precipitate
was filtered off, washed with H2O, and dried to give 2.07 g (92%) of
pure 3a.
Melting point:
82每85 ∼C, off-white crystals.
IR (KBr) [5]: 1758 cm−1 (C=O).
1H NMR (300 MHz, CDCl3)
[6]: 汛 (ppm) 7.90 (s, 1H, H-5), 7.57 (m, 2H, Ph H-2,6), 7.43 (m, 2H, Ph H-3,5), 7.29 (m, 1H, Ph H-4), 2.38 (s,
3H, CH3).
13C NMR (75 MHz, CDCl3)
[6]: 汛 (ppm) 167.6 (CO, 2J(CO,CH3) = 7.1 Hz), 154.0
(C-3, 3J(C-3,H-5) = 9.4
Hz), 139.2 (Ph C-1), 129.5 (Ph C-3,5), 128.4 (C-5, 1J = 194.3 Hz), 127.0 (Ph C-4), 118.5 (Ph
C-2,6), 87.7 (C-4, 2J(C-4,H-5)
= 5.1 Hz), 20.4 (CH3, 1J = 131.0 Hz).
15N NMR (50 MHz, CDCl3)
[7]: 汛 (ppm) −177.0 (N-1); N-2 not found.
MS (m/z, %)
[8]: 282 (M+, 6), 280 (M+, 6), 240 (100), 238 (99), 104
(49), 77 (84), 51 (30), 43 (52).
Elemental
Analysis: Calculated for C11H9BrN2O2
(281.11): C, 47.00%; H, 3.23%; N, 9.97%. Found: C, 46.74%; H, 3.07%; N, 9.84%.
4-Bromo-1-(4-bromophenyl)-1H-pyrazol-3-yl acetate (3b)
Dibromopyrazole 2b (1.27 g, 4 mmol) and excess acetic
anhydride (15 mL) were refluxed for 30 min. Then H2O
(10 mL) was added and the solution was stirred for
further 30 min. The mixture was poured into ice-water (50 mL)
and stirred for 30 min. Then the precipitate was filtered off, washed with H2O,
and dried to give 1.17 g (81%) of pure 3b.
Melting point: 77 ∼C, beige powder.
IR (KBr) [5]: 1780, 1761 cm−1 (C=O).
1H NMR (300 MHz, CDCl3)
[6]: 汛 (ppm) 7.87 (s, 1H, H-5), 7.55 (m, 2H, Ph H-3,5), 7.46 (m, 2H, Ph H-2,6), 2.38 (s, 3H, CH3).
13C NMR (75 MHz, CDCl3)
[6]: 汛 (ppm) 167.5 (CO, 2J(CO,CH3) = 7.1 Hz), 154.4
(C-3, 3J(C-3,H-5) = 9.4
Hz), 138.3 (Ph C-1), 132.6 (Ph C-3,5), 128.3 (C-5, 1J = 194.3 Hz), 120.4 (Ph C-4), 120.0 (Ph
C-2,6), 88.4 (C-4, 2J(C-4,H-5)
= 5.0 Hz), 20.4 (CH3, 1J = 130.7 Hz).
15N NMR (50 MHz, CDCl3)
[7]: 汛 (ppm) −99.2 (N-2), −179.3 (N-1).
MS (m/z, %)
[8]: 362 (M+, 1), 360 (M+, 3), 358 (M+, 1),
320 (28), 318 (60), 316 (28), 157 (26), 155 (25), 76 (29), 75 (30), 43 (100).
Elemental
Analysis: Calculated for C11H8Br2N2O2
(360.00): C, 36.70%; H, 2.24%; N, 7.78%. Found: C, 36.82%; H, 2.19%; N, 7.76%.
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